of Work: Research during the past year focused on defining the molecular mechanisms underlying the development of the mammalian olfactory system. Particular emphasis was placed on the identification of molecules which direct the establishment of the precise patterns of synaptic connectivity observed between the peripheral sensory neurons and their target neurons in the olfactory bulb. To identify molecules involved in this process, RT-PCR experiments were performed with RNA derived from neonatal olfactory epithelium and bulb tissues. Degenerate PCR primers were designed to amplify members of either the netrin, semaphorin, eph receptor-type kinase or LERK gene families. These gene families were selected for study based on their involvement in axonal guidance and/or target recognition in other systems. Using this approach, members of each of these gene families were isolated and, subsequently, cloned and sequenced. In situ hybridization studies indicated that several of these genes are highly expressed in the olfactory system. Of particular interest was the finding that some of these genes are expressed early in development during the time when synaptogenesis between olfactory sensory neurons and the olfactory bulb mitral cells is occurring. Furthermore, in some cases genes belonging to the same family were differentially expressed by different cell types; both mitral cell specific and olfactory sensory neuron specific expression patterns were observed. A second focus of research was the molecular characterization of odorant receptors. In order to examine the functional properties of odorant receptors including ligand specificity, G-protein coupling and selectivity, and ligand-dependent modifications, we are currently developing a heterologous cell expression system. Mammalian expression vectors containing the complete coding regions of three odorant receptors were constructed, and stable transfected cell lines were established. Cell lines producing high levels of odorant receptor mRNA are currently being evaluated for the production of functional odorant receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Intramural Research (Z01)
Project #
1Z01DC000034-01
Application #
6161760
Study Section
Special Emphasis Panel (LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Institute on Deafness and Other Communication Disorders
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Bartel, Dianna L; Sullivan, Susan L; Lavoie, Elise G et al. (2006) Nucleoside triphosphate diphosphohydrolase-2 is the ecto-ATPase of type I cells in taste buds. J Comp Neurol 497:1-12
LopezJimenez, Nelson D; Cavenagh, Margaret M; Sainz, Eduardo et al. (2006) Two members of the TRPP family of ion channels, Pkd1l3 and Pkd2l1, are co-expressed in a subset of taste receptor cells. J Neurochem 98:68-77
LopezJimenez, Nelson D; Sainz, Eduardo; Cavenagh, Margaret M et al. (2005) Two novel genes, Gpr113, which encodes a family 2 G-protein-coupled receptor, and Trcg1, are selectively expressed in taste receptor cells. Genomics 85:472-82
Sullivan, Susan L (2002) Mammalian chemosensory receptors. Neuroreport 13:A9-17
Sainz, E; Korley, J N; Battey, J F et al. (2001) Identification of a novel member of the T1R family of putative taste receptors. J Neurochem 77:896-903
Li, H; Wu, D K; Sullivan, S L (1999) Characterization and expression of sema4g, a novel member of the semaphorin gene family. Mech Dev 87:169-73